NM_006265.3:c.1162-7_1162-6dupTT

Variant names:

• chr8-116852713-T-TAA
• rs369816312
• NM_006265.3:c.1162-7_1162-6dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_006265.3(RAD21):​c.1162-7_1162-6dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,167,612 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (0 hom.)
• Consequence: RAD21 NM_006265.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

Genes affected

RAD21 (HGNC:9811): (RAD21 cohesin complex component) The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad21, a gene involved in the repair of DNA double-strand breaks, as well as in chromatid cohesion during mitosis. This protein is a nuclear phospho-protein, which becomes hyperphosphorylated in cell cycle M phase. The highly regulated association of this protein with mitotic chromatin specifically at the centromere region suggests its role in sister chromatid cohesion in mitotic cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00102 (138/135358) while in subpopulation AMR AF= 0.00267 (36/13492). AF 95% confidence interval is 0.00198. There are 0 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD21	NM_006265.3	c.1162-7_1162-6dupTT		splice_region_variant, intron_variant	Intron 9 of 13	ENST00000297338.7	NP_006256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7	c.1162-7_1162-6dupTT		splice_region_variant, intron_variant	Intron 9 of 13	1	NM_006265.3	ENSP00000297338.2

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 138 AN: 135316 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000431

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00267

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000938

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.000534

GnomAD3 exomes AF: 0.00170 AC: 148 AN: 87152 Hom.: 0 AF XY: 0.00165 AC XY: 80 AN XY: 48372

Gnomad AFR exome AF: 0.00151

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00201

Gnomad EAS exome AF: 0.00126

Gnomad SAS exome AF: 0.00362

Gnomad FIN exome AF: 0.000936

Gnomad NFE exome AF: 0.00160

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.00213 AC: 2202 AN: 1032254 Hom.: 0 Cov.: 2 AF XY: 0.00209 AC XY: 1059 AN XY: 507726

Gnomad4 AFR exome AF: 0.00344

Gnomad4 AMR exome AF: 0.00195

Gnomad4 ASJ exome AF: 0.000717

Gnomad4 EAS exome AF: 0.000587

Gnomad4 SAS exome AF: 0.00365

Gnomad4 FIN exome AF: 0.000823

Gnomad4 NFE exome AF: 0.00216

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00102 AC: 138 AN: 135358 Hom.: 0 Cov.: 31 AF XY: 0.00106 AC XY: 69 AN XY: 65278

Gnomad4 AFR AF: 0.000431

Gnomad4 AMR AF: 0.00267

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000942

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00131

Gnomad4 OTH AF: 0.000530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs369816312; hg19: chr8-117864952;